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Published on: December 11, 2007
Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells
1Cancer Biology Program, Hematology/Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Insights
A novel subset of human CD4-CD8- T cells, expressing invariant Valpha24-JalphaQ T cell receptor (TCR) chains, are CD1d reactive. These cells are distinct from natural killer (NK) cells and possess important immunological functions.
Area of Science:
- Immunology
- Cell Biology
- T Cell Receptor Research
Background:
- A unique subset of T cells lacking CD4 and CD8 co-receptors has been identified.
- These cells express an invariant T cell receptor (TCR) alpha chain (Valpha24-JalphaQ) paired with Vbeta11.
- They express NK locus-encoded C-type lectins but lack typical NK cell markers.
Purpose of the Study:
- To characterize the function and specificity of invariant Valpha24+ CD4-CD8- T cells.
- To determine if these cells are CD1d reactive and how they differ from NK cells.
- To investigate the immunological significance of this conserved T cell population.
Main Methods:
- TCR sequencing to analyze CDR3 diversity.
- Flow cytometry to assess cell surface marker expression (NKR-P1A, CD94, CD69, KIRs, CD16, CD56, CD57).
- Functional assays involving stimulation with anti-CD3 or CD1d, followed by cytokine production analysis (Th1/Th2).
Main Results:
- Invariant Valpha24+ Vbeta11+ T cell clones exhibited TCR-beta CDR3 diversity.
- These cells recognized the MHC class I-like CD16 molecule and discriminated between CD1d and related CD1 proteins in a TCR-mediated manner.
- Activation by anti-CD3 or CD1d induced production of both Th1 and Th2 cytokines.
- Unlike NK cells, they did not express killer inhibitory receptors (KIRs), CD16, CD56, or CD57.
Conclusions:
- Human invariant Valpha24+ CD4-CD8- T cells are CD1d reactive.
- These cells are functionally distinct from NK cells.
- The cross-species conservation of this cell population and its CD1d ligand suggests a critical immunological role.
Abstract:
A subset of human CD4-CD8- T cells that expresses an invariant Valpha24-JalphaQ T cell receptor (TCR)-alpha chain, paired predominantly with Vbeta11, has been identified. A series of these Valpha24 Vbeta11 clones were shown to have TCR-beta CDR3 diversity and express the natural killer (NK) locus-encoded C-type lectins NKR-P1A, CD94, and CD69. However, in contrast to NK cells, they did not express killer inhibitory receptors, CD16, CD56, or CD57. All invariant Valpha24(+) clones recognized the MHC class I-like CD16 molecule and discriminated between CD1d and other closely related human CD1 proteins, indicating that recognition was TCR-mediated. Recognition was not dependent upon an endosomal targeting motif in the cytoplasmic tail of CD1d. Upon activation by anti-CD3 or CD1d, the clones produced both Th1 and Th2 cytokines. These results demonstrate that human invariant Valpha24+ CD4-CD8- T cells, and presumably the homologous murine NK1+ T cell population, are CD1d reactive and functionally distinct from NK cells. The conservation of this cell population and of the CD1d ligand across species indicates an important immunological function.
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